2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Details
- Name
- 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
- Kind
- protein
- Synonyms
- 4.6.1.12
- MECDP-synthase
- mecS
- ygbB
- Gene Name
- ispF
- UniProtKB Entry
- P62617Swiss-Prot
- Organism
- Escherichia coli (strain K12)
- NCBI Taxonomy ID
- 83333
- Amino acid sequence
>lcl|BSEQ0012860|2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase MRIGHGFDVHAFGGEGPIIIGGVRIPYEKGLLAHSDGDVALHALTDALLGAAALGDIGKL FPDTDPAFKGADSRELLREAWRRIQAKGYTLGNVDVTIIAQAPKMLPHIPQMRVFIAEDL GCHMDDVNVKATTTEKLGFTGRGEGIACEAVALLIKATK
- Number of residues
- 159
- Molecular Weight
- 16897.37
- Theoretical pI
- 6.51
- GO Classification
- Functions2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity / identical protein binding / manganese ion binding / metal ion binding / zinc ion bindingProcessesisopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway / terpenoid biosynthetic process / ubiquinone biosynthetic process
- General Function
- Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.
- Specific Function
- 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity
- Pfam Domain Function
- YgbB (PF02542)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Not Available
- Gene sequence
>lcl|BSEQ0012861|2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF) ATGCGAATTGGACACGGTTTTGACGTACATGCCTTTGGCGGTGAAGGCCCAATTATCATT GGTGGCGTACGCATTCCTTACGAAAAAGGATTGCTGGCGCATTCTGATGGCGACGTGGCG CTCCATGCGTTGACCGATGCATTGCTTGGCGCGGCGGCGCTGGGGGATATCGGCAAGCTG TTCCCGGATACCGATCCGGCATTTAAAGGTGCCGATAGCCGCGAGCTGCTACGCGAAGCC TGGCGTCGTATTCAGGCGAAGGGTTATACCCTTGGCAACGTCGATGTCACTATCATCGCT CAGGCACCGAAGATGTTGCCGCACATTCCACAAATGCGCGTGTTTATTGCCGAAGATCTC GGCTGCCATATGGATGATGTTAACGTGAAAGCCACTACTACGGAAAAACTGGGATTTACC GGACGTGGGGAAGGGATTGCCTGTGAAGCGGTGGCGCTACTCATTAAGGCAACAAAATGA
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P62617 UniProtKB Entry Name ISPF_ECOLI GenBank Protein ID 433711 GenBank Gene ID L07942 PDB ID(s) 1GX1, 1H47, 1H48, 1JY8, 1KNJ, 1KNK, 1U3L, 1U3P, 1U40, 1U43, 1YQN, 2AMT, 2GZL, 3ELC, 3EOR, 3ERN, 3ESJ, 3FBA KEGG ID ecj:JW2716 NCBI Gene ID 945057 - General References
- Li C, Ichikawa JK, Ravetto JJ, Kuo HC, Fu JC, Clarke S: A new gene involved in stationary-phase survival located at 59 minutes on the Escherichia coli chromosome. J Bacteriol. 1994 Oct;176(19):6015-22. [Article]
- Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F: Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2486-90. [Article]
- Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
- Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
- Fountoulakis M, Takacs MF, Berndt P, Langen H, Takacs B: Enrichment of low abundance proteins of Escherichia coli by hydroxyapatite chromatography. Electrophoresis. 1999 Aug;20(11):2181-95. [Article]
- Campbell TL, Brown ED: Characterization of the depletion of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase in Escherichia coli and Bacillus subtilis. J Bacteriol. 2002 Oct;184(20):5609-18. [Article]
- Bitok JK, Meyers CF: 2C-Methyl-d-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity. ACS Chem Biol. 2012 Oct 19;7(10):1702-10. doi: 10.1021/cb300243w. Epub 2012 Aug 6. [Article]
- Richard SB, Ferrer JL, Bowman ME, Lillo AM, Tetzlaff CN, Cane DE, Noel JP: Structure and mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase. An enzyme in the mevalonate-independent isoprenoid biosynthetic pathway. J Biol Chem. 2002 Mar 8;277(10):8667-72. Epub 2002 Jan 10. [Article]
- Steinbacher S, Kaiser J, Wungsintaweekul J, Hecht S, Eisenreich W, Gerhardt S, Bacher A, Rohdich F: Structure of 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. J Mol Biol. 2002 Feb 8;316(1):79-88. [Article]
- Kemp LE, Bond CS, Hunter WN: Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. Epub 2002 May 7. [Article]
- Kemp LE, Alphey MS, Bond CS, Ferguson MA, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN: The identification of isoprenoids that bind in the intersubunit cavity of Escherichia coli 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase by complementary biophysical methods. Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):45-52. Epub 2004 Dec 17. [Article]
- Sgraja T, Kemp LE, Ramsden N, Hunter WN: A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 1;61(Pt 7):625-9. Epub 2005 Jun 30. [Article]
- Crane CM, Kaiser J, Ramsden NL, Lauw S, Rohdich F, Eisenreich W, Hunter WN, Bacher A, Diederich F: Fluorescent inhibitors for IspF, an enzyme in the non-mevalonate pathway for isoprenoid biosynthesis and a potential target for antimalarial therapy. Angew Chem Int Ed Engl. 2006 Feb 6;45(7):1069-74. [Article]
- Ramsden NL, Buetow L, Dawson A, Kemp LA, Ulaganathan V, Brenk R, Klebe G, Hunter WN: A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy. J Med Chem. 2009 Apr 23;52(8):2531-42. doi: 10.1021/jm801475n. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Geranyl Diphosphate experimental unknown target Details